TABLE 2.
Molecular mechanisms of naturally derived flavones against ulcerative colitis.
| Name | Model | Effective dosage | Route of administration | Mechanism of action | References |
|---|---|---|---|---|---|
| Acacetin | DSS elicited UC in C57BL/6 mice | 50, 150 mg/kg | Oral gavage | Up: Firmicutes; Turicibacter Down: TNF-α; IL-6; IL-1β; COX-2; iNOS; Bacteroidaceae; Deferribacteres; Deferribacteraceae; Enterobacteriaceae; Escherichia-Shigella; Faecalibaculum; Proteobacteria | Ren et al. (2021) |
| Apigenin | TNBS or DSS induced UC in Wistar rats or C57BL/6 mice | 1, 3 and 10 mg/kg | Dietary administration | Down: MMP-3; TNF-α; IL-6; IL-1β; IL-18; COX-2; mPGES; iNOS; NALP3; Cl-caspase-1; pro-caspase-11; Cl-caspase-11 | Marquez-Flores et al. (2016) |
| Baicalein | TNBS or DSS evoked UC in Balb/c mice or ICR mice or C57BL/6 mice | 10, 20, 40 mg/kg in vivo | Oral administration (in vivo) | Up: ZO-1; occludin; IκBα; CYP1A1; CD4+ CD25+ Foxp3+ T cells; IL-10; IL-22; TGF-β; AhR (nuclear); RORγt+ IL-22 ILC3 | Li et al. (2021g); Liu et al. (2020a); Luo et al. (2017); Yao et al. (2020); Zhong et al. (2019) |
| LPS stimulated THP-1 cells and RAW264.7 cells | 10, 25, 50 μM in vitro | Down: MPO; NO; iNOS; COX-2; ICAM-1; MCP-1; TNF-α; IL-1α; IL-1β; IL-6; IL-17; IL-17A; TLR4; MyD88; p-IκBα; p65; p-p65; p-p38; p-IRAK-1; p-JNK; p-ERK; NLRP3; ASC; caspase-1; MD-2/TLR4; Cyclin D1; STAT3; p-STAT3; IKKβ; CD11b+ cells; NOD2; SphK1; S1PR1; CD4+ IL-17+ T cells; AhR (cytosol) | |||
| Baicalin | TNBS or DSS induced UC in SD rats or C57BL/6 mice | 25, 50, 100, 120, 150 mg/kg in vivo | Oral gavage (in vivo) | Up: ZO-1; occludin; SOD; CAT; GSH; GSH-Px; IκB-α; IL-10; Bcl-2; FOXP3; β-catenin; CD4+CD25+ Foxp3+ cells; Firmicutes; Bacteroidaceae; Christensenellaceae; Peptosreptococcaceae; Ruminococcaceae; Clostridiales; acitric acid; butyric acid; propionic acid; Butyricimonas spp.; Roseburia spp., Subdoligranulum spp.; Eubacteriu spp. | Shen et al. (2019); Zhang et al. (2017); Zhu et al. (2020a); Zhu et al. (2020b) |
| LPS stimulated RAW264.7 cells or HT-29 cells | 5, 10, 20, 40 μM, 100 ng/mL in vitro | Down: MPO; NO; TNF-α; IL-1β; IL-6; IL-17; IL-33; p65; p-p65; p-IκBα; MDA; PGE2; caspase-3; caspase-9; Bax; Bcl-2/Bax; Cyt-c; p-IKKβ/IKKβ; p-IKBα/IKBα; RORγt; CD4+ IL17+ cells; Th17/Treg; p-PI3K/PI3K; p-AKT/AKT; Fas; FasL; Proteobacteria; Actinobacteria | |||
| Chrysin | DSS evoked UC in C57BL/6 mice | 25 mg/kg | Oral gavage | Up: IκBα; Cyp3a11; MDR1 | Dou et al. (2013) |
| Down: p-p65; p-IκBα; iNOS; COX-2; ICAM-1; TNF-α; MCP-1; IL-6; MPO | |||||
| Diosmetin | TNBS evoked UC in Wistar rats | 25, 50, 100, and 200 mg/kg in vivo | Oral gavage (in vivo) | Up: ZO-1; occludin; claudin-1; TEER; SOD; CAT; GSH-Px; GSH; circ-Sirt1; Sirt1; total Nrf2; nuclear Nrf2; HO-1; Bacteroidetes; Cyanobacteria; Odoribacteraceae; Prevotella; Rikenellaceae; Ruminococcus; Coprococcus; Roseburia; Oscillospira, Anaeroplasma; Synergistales | Li et al. (2021d); Yu and Liu (2021) |
| DSS evoked UC in C57BL/6 mice | 25, 50, and 100 μM in vitro | Down: MDA; TNF-α; IL-1β; IL-6; IFN-γ; NF-κB; acetyl-NF-κB; apoptotic index; COX-2; Firmicutes; Eggerthella; Flavobacterium; Clostridium | |||
| LPS stimulated Caco-2 and IEC-6 cells | |||||
| Diosmin | TNBS induced UC in Wistar rats | 5, 10, 25, and 50 mg/kg | Oral administration | Up: GSH | Shalkami et al. (2018) |
| AA induced UC in Swiss albino rats | Down: TNF-α; COX-2; MPO; MDA; caspase-3 | ||||
| Eupatilin | DSS evoked UC in C57BL/6 mice | 10, 20 mg/kg in vivo | Oral administration (in vivo) | Up: ZO-1; occludin; IκB; p-AMPK/AMPK | Zhou et al. (2018) |
| LPS induced THP-M macrophage TNF-α damaged NCM460 cells | 5 and 10 μM in vitro | Down: TNF-α; IL-1β; MPO; ROS; NOX4; p-ERK/ERK; p-pJNK/pJNK; p-p38/p38; p-p65/p65 | |||
| Fortunellin | TNBS elicited UC in SD rats | 20 and 80 mg/kg | Gavage administration | Up: SOD; GSH; Bcl-2; p-Akt; miR-374a; TEER | Xiong et al. (2018) |
| Down: IL-6; TNF-α; IL-1β; MPO; MDA; ROS; PTEN; Cl-caspase-3; Bax; p-GSK-3β | |||||
| Licoflavone B | DSS elicited UC in C57BL/6 mice | 40, 80 and 120 mg/kg | Oral administration | Up: ZO-1; occludin; claudin-1; IL-10; Bacteroidetes; Lactobacillus; Ileibacterium; Enterobacter; Vibrionaceae; Faecalibacterium; Tannerellaceae; Adlercreutzia; Ahniella; WX65; Faecalibaculum; Rhodanobacteraceae; Streptococcus; Micromonospora; Bacteroides; Eubacterium_coprostanoligenes; Parabacteroides | Zhang et al. (2022) |
| Down: IL-4; IL-6; TNF-α; IL-1β; p-ERK; p-p38; p-JNK; p-ERK/ERK; Firmicutes; Firmicutes/Bacteroidetes; Enterococcus; Alloprevotella; Eubacterium_ruminantium_group | |||||
| Linarin | DSS evoked UC in C57BL/6J mice | 25 and 50 mg/kg | Oral gavage | Up: mucin 2; ZO-1; occludin; claudin-1; IL-10; acetic acid; butyric acid; propionic acid; isobutyric acid; isovaleric acid; valeric acid | Jin et al. (2022) |
| Down: MPO; IL-6; IFN-γ; TNF-α; IL-1β | |||||
| Lonicerin | DSS evoked UC in C57BL/6 mice | 3, 10, and 30 mg/kg in vivo | Oral administration (in vivo) | Up: ATG5; NF-κB p65 (cytosol); LC3B-I/II | Lv et al. (2021) |
| LPS stimulated THP-1 or BMDMs cells | 1, 3, 10, and 30 μM in vitro | Down: MPO; F4/80+ macrophages; Cl-caspase-1; IL-1β; IL-18; IL-6; TNF; IL-1; NLRP3; EZH2; NF-κB p65 (nuclear); p-p65; p62 | |||
| Luteolin | DSS elicited UC in C57BL/6 mice or Wistar rat | 5, 10, 20, 50 and 100 mg/kg in vivo | Oral administration (in vivo) | Up: ZO-1; occludin; claudin 1; TEER; SOD; CAT; Nrf2; HO-1; NQO1; p-ERK1/2; proliferating cells/crypt; SHP-1; PPAR-γ; Bacteroidetes; Bacteroidaceae; Lactobacillus; Lachnospiraceae_NK4A136_group; Roseburia; Bacteroides; Butyricicoccus; arginine metabolism; proline metabolism; starch metabolism; sucrose metabolism | Li et al. (2016); Li et al. (2021a); Li et al. (2021b); Suga et al. (2021); Vukelic et al. (2020); Zuo et al. (2021) |
| TNF-α, and IFN-γ stimulated Caco-2 cells 5-HT stimulated RBL-2H3 cells | 25, 50, 100, and 150 μM in vitro | Down: MDA; TNF-α; IL-1β; IL-6; p-JNK1/2; p-p38; p-Akt; p-STAT3; NF-κB p65; TNF-α; COX-2; Cl-caspase-3; caspase-9; Cl-caspase-9; cleaved PARP; p21; LC3B-II; Atg5; HMGB1; TLR4; MyD88; p-p65/p65; TPH-1; 5-HT; CLDN2; p-STAT3; STAT3; IL-17; IL-23; Firmicutes; Proteobacteria; Prevotella_9; the ability of DNA repair; ribosome metabolism; purine metabolism | |||
| Nobiletin | TNBS elicited UC in SD rats | 20, 40 and 50 mg/kg in vivo 10, 20, 40 and 80 μM in vitro | Oral administration (in vivo) | Down: TEER; MPO; mast cells; TNF-α; IL-1β; IL-6; NO; PGE2; iNOS; COX-2; MLCK; p65; PI3K; p-Akt; CCL2; COL13A1 | Hagenlocher et al. (2019); Xiong et al. (2015) |
| IL-10−/− BALB/c mice | |||||
| LPS stimulated Caco-2 cells | |||||
| LPS stimulated human intestinal fibroblasts | |||||
| Oroxylin A | DSS evoked UC in C57BL/6 mice | 100 and 200 mg/kg in vivo | Dietary administration (in vivo) | Up: p65 (cytoplasm), IκBα | Zhou et al. (2017) |
| LPS combined ATP stimulated THP-Ms or BMDMs cells | 25, 50 and 100 μM in vitro | Down: MPO; iNOS; TNF-α; IL-6; IL-1β; NLRP3; F4/80; p65; p-IκBα; Cl-IL-1β; Cl-caspase-1; ASC speck formation | |||
| Pectolinarigenin | DSS elicited UC in C57BL/6J mice | 2.5, 5 and 10 mg/kg in vivo | Oral administration (in vivo) | Up: Nrf2; IκBα; SOD; CAT; GSH; mucin 2 | Feng et al. (2022) |
| LPS stimulated RAW 264.7 and THP1 cell lines | 10 and 20 μM in vitro | Down: NF-κB p-p65; p-IκBα; COX-2; iNOS; IL-6; IL-1β; TNF-α; MPO; MDA | |||
| Sinensetin | TNBS evoked UC in SD rats | 20 and 80 mg/kg in vivo | Oral gavage (in vivo) | Up: TEER; LC3Ⅱ/Ⅰ; p-ULK1; AMPK; p-AMPK | Xiong et al. (2019) |
| TNF-α stimulated Caco-2 cells | 20 and 40 μM in vitro | Down: IL-1β; IL-6; IFN-γ; MPO; p62; claudin-2; Cl-capsase-3; Cl-capsase-9 | |||
| Tangeretin | TNBS evoked UC in C57BL/6 mice | 10 or 20 mg/kg in vivo | Oral administration (in vivo) | Up: ZO-1; occludin; claudin-1; IL-10; Foxp3; Tregs differentiation; Firmicutes; Lachnospiraceae; Lactobacillaceae; valeric; acetic acids; butyric acids | Chen et al. (2021a); Eun et al. (2017) |
| LPS stimulated DCs | 5, 10, and 20 μM in vitro | Down: TNF-α; IL-1β; IL-12; IL-17; IL-23; IL-12/IL-10; TNF-α/IL-10; IFN-γ; iNOS; COX-2; MPO; differentiation of Th1 and Th17 cells; MHC Ⅱ; CD40; CD80; CD86; p-p65; T-bet; RORγt; p-TAK1; p-IκBα; p-IRAK1; p-IKK-α/β; p-p38; p-ERK; p-JNK; Bacteroidetes; Rikenellaceae; Marinifilaceae; Enterobacteriaceae; Rikenellaceae_RC9_gut_group; Alistipes | |||
| Tricin | DSS evoked UC in BALB/c mice | 75, 100 and 150 mg/kg in vivo | Oral gavage (in vivo) | Up: Bacteroidetes | Li et al. (2021f) |
| LPS stimulated RAW264.7 cells | 12.5, 25 and 50, μM in vitro | Down: Nitrite; TNF-α; IL-1β; IL-6; MIP-2; MPO; MDSC; Treg cells; p-p65; Firmicutes; Proteobacteria; Deferribacteres; Helicobacter; Ruminiclostridium_5; Streptococcus; Veillonella; Mucispirillum; Klebsiella; Haemophilus | |||
| Wogonin | DSS induced UC in BALB/c mice | 30 mg/kg | Oral gavage | Up: SOD; GST; GSH; IL-10; Bax; caspas-3; caspas-9; Nrf2; HO-1 | Zhou et al. (2022) |
| Down: MPO; NO; TBARS; TNF-α; IL-6; PGE2; Bcl-2; COX-2; iNOS; TLR4; p-p65 | |||||
| Wogonoside | DSS evoked UC in Balb/C or C57BL/6 mice | 12.5, 25 and 50 mg/kg in vivo | Oral gavage (in vivo) | Up: ZO-1; occludin; claudin1; TEER; NF-κB (cytoplasm); TXNIP | Huang et al. (2020); Liu et al. (2020b); Sun et al. (2015) |
| LPS stimulated THP-1 cells TNF-α stimulated Caco-2 cells | 12.5, 25 and 50 μM in vitro | Down: MPO; iNOS; TNF-α; IL-1β; IL-6; IL-13; IL-18; IFN-γ; MIP-1α; NF-κB (nucleus); p-IκBα; p-p65; Cl-caspase-1; pro-caspase-1; Cl-caspase-1/pro-caspase-1; Cl-IL-1β; NLRP3; ASC; CD11b+F4/80+ monocyte/macrophages; CD11b+Gr-1+ neutrophils; F4/80+ cells; pMLC2/MLC2; MLCK |